Recently, we have discovered that a brain substance which binds to anti-prolactin immune serum increases the estrogen-dependent behavior, lordosis, in female rats, raising the possibility that part of the nerual action of estrogen is mediated through cells containing this prolactin-like substance. The proposed research focuses primarily on the hypothalamus to midbrain connection, which is critically involved in mediating estrogen-dependent effects on lordosis and which contains immunoreactive prolactin. Specifically, we will perform behavioral experiments in female rats to explore further the role of a prolactin-like substance in lordosis. We will provide a comprehensive description of the distribution of immunoreactive prolactin in male and female rat brains, at the light microscopic level. the apparent molecular weight and isoelectric point of the prolactin-like substance will be determined by electrophoresis of immunoprecipitated brain homogenates from intact and hypophysectomized rats. We will study the possible effects of gonadal hormones on the content of prolactin-like substance in the brain by exploring whether hormones alter the amount of immunoreactive prolactin in cell bodies and fibers. By combining immunocytochemistry with autoradiography, we will determine whether cells producing the prolactin-like substance also concentrate estrogen. We have preliminary evidence that the prolactin gene is expressed in the brain. Due to the substantial amount of information available on the prolactin gene, the neuronal system containing immunoreactive prolactin may become one of the best characterized brain pathways. These studies should provide new knowledge of the mechanisms by which gonadal steroids act on the brain, the long-term objective of this research. In humans, steroid hormone action on the brain regulates fertility and reproductive senescence and can exacerbate several neurological problems, such as chorea, Parkinsonism and epilepsy.